RT Journal Article
SR Electronic
T1 A genome-wide association study of rheumatoid arthritis without antibodies against citrullinated peptides
JF Annals of the Rheumatic Diseases
JO Ann Rheum Dis
FD BMJ Publishing Group Ltd and European League Against Rheumatism
SP e15
OP e15
DO 10.1136/annrheumdis-2013-204591
VO 74
IS 3
A1 L Bossini-Castillo
A1 C de Kovel
A1 H Kallberg
A1 R van ‘t Slot
A1 A Italiaander
A1 M Coenen
A1 P P Tak
A1 M D Posthumus
A1 C Wijmenga
A1 T Huizinga
A1 A H M van der Helm-van Mil
A1 G Stoeken-Rijsbergen
A1 Luis Rodriguez-Rodriguez
A1 Alejandro Balsa
A1 Isidoro González-Álvaro
A1 Miguel Ángel González-Gay
A1 Carmen Gómez-Vaquero
A1 B Franke
A1 LifeLines Cohort Study
A1 S Vermeulen
A1 IE van der Horst-Bruinsma
A1 B A C Dijkmans
A1 G J Wolbink
A1 R A Ophoff
A1 M T Maehlen
A1 P van Riel
A1 M Merriman
A1 L Klareskog
A1 B A Lie
A1 T Merriman
A1 J B A Crusius
A1 E Brouwer
A1 J Martin
A1 N de Vries
A1 R Toes
A1 L Padyukov
A1 B P C Koeleman
YR 2015
UL http://ard.bmj.com/content/74/3/e15.abstract
AB Introduction Rheumatoid arthritis (RA) patients can be classified based on presence or absence of anticitrullinated peptide antibodies (ACPA) in their serum. This heterogeneity among patients may reflect important biological differences underlying the disease process. To date, the majority of genetic studies have focused on the ACPA-positive group. Therefore, our goal was to analyse the genetic risk factors that contribute to ACPA-negative RA. Methods We performed a large-scale genome-wide association study (GWAS) in three Caucasian European cohorts comprising 1148 ACPA-negative RA patients and 6008 controls. All patients were screened using the Illumina Human Cyto-12 chip, and controls were genotyped using different genome-wide platforms. Population-independent analyses were carried out by means of logistic regression. Meta-analysis with previously published data was performed as follow-up for selected signals (reaching a total of 1922 ACPA-negative RA patients and 7087 controls). Imputation of classical HLA alleles, amino acid residues and single nucleotide polymorphisms was undertaken. Results The combined analysis of the studied cohorts resulted in identification of a peak of association in the HLA-region and several suggestive non-HLA associations. Meta-analysis with previous reports confirmed the association of the HLA region with this subset and an observed association in the CLYBL locus remained suggestive. The imputation and deep interrogation of the HLA region led to identification of a two amino acid model (HLA-B at position 9 and HLA-DRB1 at position 11) that accounted for the observed genome-wide associations in this region. Conclusions Our study shed light on the influence of the HLA region in ACPA-negative RA and identified a suggestive risk locus for this condition.